Pharmacotherapy for opioid use disorder in pregnancy.

PURPOSE OF REVIEW: Opioid use disorder (OUD) in pregnancy has significantly increased in the last decade, impacting 8.2 per 1000 deliveries. OUD carries significant risk of morbidity and mortality for both the birthing person and neonate, but outcomes for both are improved with opioid agonist treatment (OAT). Here, we describe the recommended forms of OAT in pregnancy, updates to the literature, and alternate OAT strategies, and share practical peripartum considerations for patients on OAT. RECENT FINDINGS: Recent studies comparing buprenorphine and methadone have reaffirmed previous findings that buprenorphine is associated with superior outcomes for the neonate, without clear differences in morbidity or mortality for the birthing person. Optimal initiation and dosing of OAT remains unclear, with several recent studies evaluating methods of initiation, as well as a potential role for higher and more rapid dosing in the fentanyl era. Alternative products such as buprenorphine-naloxone and extended-release buprenorphine are of significant research interest, though randomized prospective data are not yet available. SUMMARY: Buprenorphine and methadone are standard of care for treatment of OUD during pregnancy, and multiple patient factors impact the optimal choice. Insufficient data exist to recommend alternative agents as a primary strategy currently. All patients with OUD in pregnancy should be counseled regarding OAT. VIDEO: http://links.lww.com/COOG/A94.

When Are Pregnant Patients Receiving Tranexamic Acid during Delivery Hospitalization in the United States?

OBJECTIVE: The World Health Organization recommends tranexamic acid (TXA) in the management of postpartum hemorrhage (PPH). However, the role of TXA in PPH prevention and the optimal timing of TXA administration remain unknown. Our objective was to describe the timing of TXA administration, differences in timing of TXA administration by mode of delivery, and current trends in TXA administration in the United States. STUDY DESIGN: We conducted a descriptive study of trends in TXA administration using the Cerner Real-World Database. We identified 1,544,712 deliveries occurring at greater than 24 weeks' gestation from January 1, 2016, to February 21, 2023. Demographic data were collected including gestational age, mode of delivery, and comorbidities. The timing of TXA administration and differences in TXA timing by mode of delivery were also collected. RESULTS: In our cohort, 21,433 patients (1.39%) received TXA. The majority of patients who received TXA were between ages 25 and 34 years old (55.3%), White (60.7%), and delivered between 37 and 416/7 weeks (81.4%). The TXA group had a higher prevalence of medical comorbidities including obesity (32.9 vs. 19.0%, p < 0.00001), preeclampsia (19.6 vs. 6.81%, p < 0.00001), and pregestational diabetes (3.27 vs. 1.36%, p < 0.00001). Among women who received TXA, 15.4% received it within 3 hours before delivery. Among patients who received TXA after delivery, 23.6% received TXA within 3 hours after delivery, whereas 35.7% received TXA between 10 and 24 hours after delivery. A total of 80.4% of patients who received TXA before delivery had a cesarean delivery. CONCLUSION: While TXA is most commonly administered after delivery, many patients are receiving TXA prior to delivery in the United States without clear evidence to guide the timing of administration. A randomized trial is urgently needed to determine the safety and efficacy of TXA when administered prior to delivery. KEY POINTS: · TXA is used in the treatment of PPH.. · The role of TXA in prevention of PPH is unclear.. · Fewer than 2% of patients in the United States receive TXA at delivery.. · TXA administration before delivery in the United States is rising..

Impact of anemia and thrombocytopenia on postpartum hemorrhage risk among women with term singleton pregnancy.

Both thrombocytopenia (platelet count < 150 × 103/µL) and anemia have been associated with postpartum hemorrhage (PPH). However, the impact of thrombocytopenia on PPH risk among women with mild and severe anemia is unknown. We sought to evaluate the association between thrombocytopenia and anemia in increasing risk of PPH. We performed a secondary analysis of a retrospective cohort of pregnant women from 19 hospitals across the United States from 2016 to 2021. Women who had a term singleton pregnancy and hematocrit (Hct) ≤ 33% at delivery were included in the study. The primary outcome was PPH (defined as blood loss ≥ 1000 mL or blood transfusion). We also analyzed the effect of severe anemia (Hct < 28%) on the association between PPH and thrombocytopenia. Chi-squared tests and Fisher's exact tests were used for categorical variables and an independent t-test was used for continuous variables. There were 20,808 women who met our inclusion criteria, of which 1793 (8.6%) had platelet count < 150 × 103/µL. The prevalence of PPH was 6.4%. Compared with women with normal platelet count, those with thrombocytopenia had 1.3-fold higher odds of PPH [6.8% vs. 4.5%, adjusted OR 1.3 (1.1-1.7)]. Platelet count ≥ 150 × 103/µL was associated with decreased odds of PPH among patients with hct between 28 and 33% and hct < 28%. In conclusion, anemic women with term singleton pregnancies who delivered with thrombocytopenia had a higher frequency of PPH. Normal platelet count at delivery was protective against PPH in the setting of anemia regardless of severity.

The Effect of Bariatric Surgery on Perioperative Complications after Hysterectomy.

STUDY OBJECTIVE: To compare intraoperative and 30-day posthysterectomy outcomes between patients who had bariatric surgery before hysterectomy and patients with a body mass index (BMI) >40 kg/m2 without a history of bariatric surgery. DESIGN: A retrospective cohort study. SETTING: A tertiary-care, academic medical center. PATIENTS: Patients with a history of bariatric surgery and patients with BMI >40 kg/m2 and no previous bariatric surgery who underwent any route of hysterectomy between January 1, 2000, and March 1, 2018. INTERVENTIONS: After exclusion of patients with gynecologic malignancy and bariatric surgery reversal, 223 patients with a history of bariatric surgery were matched at a 1:2 ratio by year of hysterectomy to 446 randomly selected patients with a BMI >40 kg/m2 and no bariatric surgery before hysterectomy. Demographics, medical comorbidities, and surgical characteristics were collected by a manual chart review. Chi-square or Fisher's exact tests were used to compare the incidence of intraoperative and 30-day postoperative complications. Polytomous logistic regression was used to estimate the odds of major and minor postoperative complications. Binary logistic regression was used to estimate the odds of any intra- or postoperative complications. MEASUREMENTS AND MAIN RESULTS: The mean BMI in the bariatric surgery group was 35.2 ± 7.9 kg/m2, compared with 46.3 ± 5.6 kg/m2 in the control group (p <.01). Fewer patients in the bariatric surgery group had obesity-related comorbidities than the group with no previous bariatric surgery (p <.01). There were lower odds of any intraoperative complication in the bariatric surgery group than in the group with no bariatric surgery (adjusted odds ratio, 0.32; 95% confidence interval [CI], 0.13-0.77), after adjusting for relevant confounding factors between groups. However, there was no difference in overall postoperative complications between women who had bariatric surgery and those who did not (adjusted odds ratio, 1.25; 95% CI, 0.82-1.91). When analyzed individually, a higher proportion of patients in the bariatric surgery group had postoperative cuff separation or dehiscence (1.4% [3/223], p = .04) and urinary retention (5.8% [13/223], p <.01). Combining all perioperative complications, we found no significant difference in minor complications, defined as Clavien-Dindo Grade 1 or 2 (adjusted odds ratio, 1.04; 95% CI, 0.68-1.60), major complications, defined as Clavien-Dindo Grade 3 or higher (adjusted odds ratio, 1.25; 95% CI, 0.61-2.54), or combined major and minor perioperative complications (adjusted odds ratio, 0.96; 95% CI, 0.63-1.44) between patients with a history of bariatric surgery and morbidly obese patients with no bariatric surgery before hysterectomy, after adjusting for relevant confounding factors between groups. CONCLUSION: Compared with women who had a BMI >40 kg/m2, patients with a history of bariatric surgery before hysterectomy had a lower odds of complications during hysterectomy. However, despite lower BMI and fewer obesity-related medical comorbidities, there was no significant difference in posthysterectomy complications and no significant differences in overall major and minor complications.

Feasibility of frequent patient-reported outcome surveillance in patients undergoing hematopoietic cell transplantation.

Patient-reported outcomes (PROs), including symptoms and health-related quality of life (HRQOL), provide a patient-centered description of hematopoietic cell transplantation (HCT)-related toxicity. These data characterize the patient experience after HCT and may have prognostic usefulness for long-term outcomes after HCT. We conducted a study of 32 patients after HCT (10 autologous HCT recipients, 11 full-intensity conditioning allogeneic HCT recipients, and 11 reduced-intensity conditioning allogeneic HCT recipients) to determine the feasibility of weekly electronic PRO collection from HCT until day (D) +100. We used questions from the PRO version of the Common Terminology Criteria for Adverse Events to capture symptoms, and the Patient-Reported Outcomes Measurement Information System Global Health scale to measure physical and mental HRQOL. The vast majority (94%) of patients used the electronic PRO system, with only 6% opting for paper-and-pencil only. The median weekly percentage of participants who completed the surveys was 100% in all cohorts through hospital discharge, and remained 100% for the autologous HCT and reduced-intensity allogeneic HCT cohorts through D+100. Patients were satisfied with the electronic system, giving high marks for readability, comfort, and questionnaire length. Symptom severity varied by absolute level and type of symptom across the 3 cohorts, with the full-intensity allogeneic HCT cohort exhibiting the greatest median overall symptom severity, peaking at D+7. Median physical health HRQOL scores decreased with time in the 3 cohorts, and HRQOL was generally correlated with overall symptom severity. Our results demonstrate the feasibility of frequent electronic PROs in the early post-HCT period. Future studies in larger populations to explore predictive models using frequent PRO data for outcomes, including long-term HRQOL and survival, are warranted.

The association between body mass index and postpartum hemorrhage after cesarean delivery.

We aimed to evaluate the association between obesity and postpartum hemorrhage (PPH) after cesarean delivery (CD). This was a retrospective cohort study using a multicenter database of 20 hospitals in the United States. We analyzed 27,708 patients undergoing CD from 2015 to 2019. The exposure of interest was BMI, and the primary outcome was PPH (estimated blood loss [EBL] ≥ 1000 mL). Simple logistic regression was used to evaluate the relationship between obesity and intrapartum complications. Multivariable logistic regression was used to adjust for any confounding demographic variables. Hosmer and Lemeshow's purposeful selection algorithm was adapted to develop a multivariable logistic regression model of PPH. Analyses were conducted using STATA 16.1 (College Station, Texas) with p ≤ 0.05 considered significant. BMI exerted a significant effect on the frequency of PPH (p = 0.004). Compared to patients with BMI 18.5-24.9 kg/m2, patients with BMI between 25 and 59.9 kg/m2 had an increased odds of PPH. The odds of PPH in patients with BMI > 60 kg/m2 was not increased compared to patients with BMI 18.5-24.9 kg/m2. Obesity was associated with a decreased odds of blood transfusion (aOR 0.73, 95% CI 0.55-0.97). In conclusion, higher BMI was associated with PPH yet a lower odds of transfusion after CD.

Chemomobilization with Etoposide is Highly Effective in Patients with Multiple Myeloma and Overcomes the Effects of Age and Prior Therapy.

The optimal mobilization strategy prior to autologous stem cell transplantation for patients with multiple myeloma remains unclear. Mobilization with cytokines alone appears to yield suboptimal results in older patients as well as patients who have received prior lenalidomide. To avoid the marked cytopenias and risks of hemorrhagic cystitis associated with the administration of cyclophosphamide, we investigated the efficacy and safety of chemomobilization with an intermediate dose etoposide (VP-16; 375 mg/m(2) on days +1 and +2) and granulocyte-colony stimulating factor (G-CSF) (5 µg/kg twice daily from day +3 through the final day of collection). We reviewed our institutional experience with 152 myeloma patients mobilized with this regimen. The addition of VP-16 to G-CSF resulted in successful mobilization in 100% of patients, including 143 (94%) who collected successfully in a single day. A total of 99% of patients, including those with prior XRT and/or prior lenalidomide or thalidomide therapy, collected at least 5 × 10(6) cells/kg in 1 or 2 days of apheresis, and the median total number of CD34(+) cells collected in the entire population was 12 × 10(6) cells/kg. Collection was predictable, with 61% of patients collecting on day +11, and the rest between days +7 and +13. There were no variables, including age, prior imid exposure, radiation therapy, or total amount of prior therapy that were associated with suboptimal mobilization. Adverse effects of the regimen included supportive transfusions required in 31 (20%) patients, and fevers requiring hospitalization or intravenous antibiotics in 26 (17%) patients. VP-16 and G-CSF appears to be a safe and effective mobilization regimen for patients with multiple myeloma undergoing autologous stem cell transplantation, producing excellent stem cell yield with the majority of patients requiring 1 day of apheresis.

Usefulness of the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) in predicting outcomes for adolescents and young adults with hematologic malignancies undergoing allogeneic stem cell transplant.

BACKGROUND: The HCT-CI helps to predict non-relapse mortality (NRM) and overall survival (OS) in allogeneic hematopoietic cell transplantation (HCT) recipients. The usefulness of this index in a younger, adolescent and young adult (AYA) population is unclear. PROCEDURE: We tested the validity of the HCT-CI as a predictor of mortality in a retrospective cohort of 56 AYA recipients between the ages of 16 and 39, using chart abstraction followed by univariable and multivariate analysis. RESULTS: Only pulmonary dysfunction (46%), hepatic dysfunction (27%), infection (20%), and psychiatric disturbance (11%) had frequencies greater than 5% in this population. HCT-CI scores of 0-2 were present in 54%, and scores of >3 in 46%. The cumulative incidence of NRM at 2 years was 32%, with an OS of 46%; the NRM and OS for patients with an HCT-CI of 0-2 were 24% and 62%, whereas the NRM and OS for patients with an HCT-CI >3 were 38% and 28%. Patients with pulmonary dysfunction prior to transplant had a 29% OS at 2 years, compared to a 61% OS among patients without (P = 0.001). There was no statistically significant difference for patients and a worse NRM (P = 0.08). In multivariable analysis, both an HCT-CI score of >3 and any pulmonary dysfunction remained associated with OS (P = 0.01, P = 0.03), but neither with NRM. CONCLUSIONS: The HCT-CI appears useful in predicting OS in AYAs, though higher scores may reflect prior treatment, with pulmonary dysfunction particularly prevalent. Prospective studies to further validate and explain these findings are warranted.

Management of hyponatraemia in pre-eclampsia with severe features.

Pre-eclampsia is a common pregnancy complication with many associated maternal and fetal risks, yet its pathophysiology remains poorly understood. Hyponatraemia is a rarely described finding in pre-eclampsia that has been associated with both maternal and fetal complications and medically indicated delivery. We present a case of hyponatraemia in a patient admitted for induction of labour for gestational hypertension, which developed into pre-eclampsia with severe features requiring magnesium sulfate therapy for seizure prophylaxis. The patient's hyponatraemia resolved with delivery, fluid restriction and serial sodium monitoring. Adjustment to the components of the patient's magnesium sulfate infusion was made to reduce free water intake and avoid further exacerbation of her hyponatraemia. While there is currently no recommendation to routinely monitor sodium levels in hypertensive disorders of pregnancy, careful consideration of this potential finding in cases of pre-eclampsia should be given due to the overlap between symptoms of hyponatraemia and cerebral symptoms of pre-eclampsia.

Oxytocin during breastfeeding and maternal mood symptoms.

This study aimed to quantify the relationship between postpartum depression and anxiety, oxytocin, and breastfeeding. We conducted a longitudinal prospective study of mother-infant dyads from the third trimester of pregnancy to 12 months postpartum. A sample of 222 women were recruited to complete the Beck Depression Inventory II and Spielberger State-Trait Anxiety Inventory-state subscale, participate in observed infant feeding sessions at 2 and 6 months postpartum, and provide venous blood samples during feeding. Maternal venous oxytocin levels in EDTA-treated plasma and saliva were determined by enzyme immunoassay with extraction and a composite measure of area under the curve (AUC) was used to define oxytocin across a breastfeeding session. Linear regression was used to estimate associations between postpartum depression and anxiety as predictors and oxytocin AUC during breastfeeding as the outcome at both 2 and 6 months postpartum. Mixed models accounting for correlations between repeated oxytocin measures were used to quantify the association between current depression and/or anxiety symptoms and oxytocin profiles during breastfeeding. We found no significant differences in oxytocin AUC across a feed between depressed or anxious women and asymptomatic women at either 2 or 6 months postpartum. Repeated measures analyses demonstrated no differences in oxytocin trajectories during breastfeeding by symptom group but possible differences by antidepressant use. Our study suggests that external factors may influence the relationship between oxytocin, maternal mood symptoms, and infant feeding.

An open-label study of the tolerability of mixed amphetamine salts in adults with attention-deficit/hyperactivity disorder and treated primary essential hypertension.

OBJECTIVE: To evaluate the short-term tolerability of an extended-release preparation of the stimulant medication mixed amphetamine salts (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) whose hypertension has been successfully treated with antihypertensive medications. METHOD: An 8-week, 2-phase, open-label study design was implemented. All adults had ADHD (DSM-IV diagnosis) and essential hypertension and were required to be normotensive (blood pressure < 135/85 mm Hg, treated) for at least 4 weeks at entry into the study. MAS XR was given for a 6-week period, titrated once each week to a target maximum dose of 60 mg/day given once daily in the morning (phase 1), and then discontinued for 2 weeks at the end of the study (phase 2). At baseline, subjects underwent a comprehensive clinical assessment, medical history, vital signs assessment, and electrocardiogram (ECG). Rating scales were used throughout the study to assess response to treatment, and blood pressure was measured manually at each study visit. The primary outcome was the effect of MAS XR on blood pressure and the development of hypertension. RESULTS: Thirteen subjects receiving antihypertensive therapy were entered and placed on MAS XR treatment and completed the trial. There were no serious adverse events. No sustained elevated blood pressure (> 140/90 mm Hg at 2 consecutive visits) was observed in the subjects treated with MAS XR. Similar rates of single episodes of hypertension were observed in phases 1 and 2. Similarly, there was no group mean increase in systolic or diastolic blood pressure or pulse during treatment with MAS XR. No clinically significant changes in the ECG were observed. During the 6-week medication phase, significant improvement was found on rating scales assessing ADHD symptoms and severity that reversed with discontinuation of MAS XR. CONCLUSION: The results of this open study suggest that adults with ADHD and controlled hypertension can be safely treated with MAS XR.

The clinical dilemma of using medications in substance-abusing adolescents and adults with attention-deficit/hyperactivity disorder: what does the literature tell us?

OBJECTIVE: Adolescents and adults with attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUD) are increasingly recognized in clinical practice. The role of pharmacological treatment for ADHD in these comorbid individuals remains unclear. METHODS: A systematic review of the medical literature was conducted through PubMed, supplemented with data from scientific presentations, to evaluate the role of medication treatment of ADHD in substance abusing individuals with ADHD. Meta-analysis was used to evaluate the effects of medication therapy on ADHD and SUD outcomes in general, while specifically addressing trial design, trial duration, retention, class of medication, age group, concurrent psychotherapy, and outcome in both SUD and ADHD domains. RESULTS: Four studies in adolescents and five studies in adults with ADHD plus SUD were identified (two controlled and seven open studies; n = 222 subjects). The standard mean difference (SMD) indicated statistically significant improvements in ADHD and SUD that were not maintained when evaluating controlled studies only. Albeit limited by power, trial duration, retention rate, and age group did not influence outcome. No worsening of SUD or drug-drug interactions were observed in any of the studies. The results could not be accounted for by any single study or by publication bias. CONCLUSION: Treating ADHD pharmacologically in individuals with ADHD plus SUD has a moderate impact on ADHD and SUD that is not observed in controlled trials and does not result in worsening of SUD or adverse interactions specific to SUD. Further controlled trials evaluating the effect of novel combinations of psychotherapy and ADHD pharmacotherapy on SUD relapse in these groups are warranted.

Do individuals with ADHD self-medicate with cigarettes and substances of abuse? Results from a controlled family study of ADHD.

Studies report increased rates of cigarette and substance use in youths with Attention-Deficit/Hyperactivity Disorder (ADHD), though the mechanism of risk remains unclear. The present study tests the hypothesis that ADHD individuals "self-medicate" with cigarettes and substances of abuse. As part of five- and ten-year case-control longitudinal family studies of ADHD, responses to the Drug Use Screening Inventory (DUSI) were examined for evidence of self-medication. DUSI data from 90 ADHD probands and 96 control probands were obtained. Thirty-six percent of subjects reported self-medication, 25% used to get high, and 39% had unknown motivation. No significant differences were found between ADHD and controls in motivation. ADHD symptoms did not differ between self-medicators and subjects using to get high. DUSI problem scores were higher in ADHD (versus controls), those using to get high (versus self-medicators), and subjects using alcohol (versus other substances). More than one-third of adolescents and young adults endorsed using cigarettes and substances for self medication. Studies clarifying the role of self-medication in substance use disorders are necessary.